rs1141608

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000202.8(IDS):c.438C>T(p.Thr146=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 1,165,083 control chromosomes in the GnomAD database, including 54,181 homozygotes. There are 119,286 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 4367 hom., 9370 hem., cov: 22)

Exomes 𝑓: 0.35 ( 49814 hom. 109916 hem. )

Consequence

IDS
NM_000202.8 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 0.771

Variant links:

Genes affected

IDS (HGNC:5389): (iduronate 2-sulfatase) This gene encodes a member of the sulfatase family of proteins. The encoded preproprotein is proteolytically processed to generate two polypeptide chains. This enzyme is involved in the lysosomal degradation of heparan sulfate and dermatan sulfate. Mutations in this gene are associated with the X-linked lysosomal storage disease mucopolysaccharidosis type II, also known as Hunter syndrome. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

IDS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant X-149501018-G-A is Benign according to our data. Variant chrX-149501018-G-A is described in ClinVar as [Benign]. Clinvar id is 92619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-149501018-G-A is described in Lovd as [Likely_benign]. Variant chrX-149501018-G-A is described in Lovd as [Likely_pathogenic]. Variant chrX-149501018-G-A is described in Lovd as [Pathogenic]. Variant chrX-149501018-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.771 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
IDS	NM_000202.8 linkuse as main transcript	c.438C>T	p.Thr146=	synonymous_variant	4/9	ENST00000340855.11	NP_000193.1
IDS	NM_001166550.4 linkuse as main transcript	c.168C>T	p.Thr56=	synonymous_variant	4/9		NP_001160022.1
IDS	NM_006123.5 linkuse as main transcript	c.438C>T	p.Thr146=	synonymous_variant	4/8		NP_006114.1
IDS	NR_104128.2 linkuse as main transcript	n.607C>T		non_coding_transcript_exon_variant	4/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IDS	ENST00000340855.11 linkuse as main transcript	c.438C>T	p.Thr146=	synonymous_variant	4/9	1	NM_000202.8	ENSP00000339801	P1	P22304-1

Frequencies

GnomAD3 genomes

AF:

0.312

AC:

34181

AN:

109470

Hom.:

4371

Cov.:

AF XY:

0.294

AC XY:

9358

AN XY:

31862

show subpopulations

Gnomad AFR

AF:

0.252

Gnomad AMI

AF:

0.407

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.331

Gnomad EAS

AF:

0.00283

Gnomad SAS

AF:

0.0690

Gnomad FIN

AF:

0.299

Gnomad MID

AF:

0.433

Gnomad NFE

AF:

0.390

Gnomad OTH

AF:

0.325

GnomAD3 exomes

AF:

0.275

AC:

50217

AN:

182867

Hom.:

5441

AF XY:

0.273

AC XY:

18400

AN XY:

67351

show subpopulations

Gnomad AFR exome

AF:

0.255

Gnomad AMR exome

AF:

0.157

Gnomad ASJ exome

AF:

0.334

Gnomad EAS exome

AF:

0.00115

Gnomad SAS exome

AF:

0.0903

Gnomad FIN exome

AF:

0.317

Gnomad NFE exome

AF:

0.391

Gnomad OTH exome

AF:

0.307

GnomAD4 exome

AF:

0.347

AC:

366356

AN:

1055561

Hom.:

49814

Cov.:

AF XY:

0.328

AC XY:

109916

AN XY:

335471

show subpopulations

Gnomad4 AFR exome

AF:

0.245

Gnomad4 AMR exome

AF:

0.165

Gnomad4 ASJ exome

AF:

0.336

Gnomad4 EAS exome

AF:

0.00110

Gnomad4 SAS exome

AF:

0.0926

Gnomad4 FIN exome

AF:

0.318

Gnomad4 NFE exome

AF:

0.392

Gnomad4 OTH exome

AF:

0.322

GnomAD4 genome

AF:

0.312

AC:

34176

AN:

109522

Hom.:

4367

Cov.:

AF XY:

0.294

AC XY:

9370

AN XY:

31922

show subpopulations

Gnomad4 AFR

AF:

0.252

Gnomad4 AMR

AF:

0.249

Gnomad4 ASJ

AF:

0.331

Gnomad4 EAS

AF:

0.00283

Gnomad4 SAS

AF:

0.0681

Gnomad4 FIN

AF:

0.299

Gnomad4 NFE

AF:

0.390

Gnomad4 OTH

AF:

0.319

Alfa

AF:

0.340

Hom.:

6734

Bravo

AF:

0.308

EpiCase

AF:

0.397

EpiControl

AF:

0.393

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:4

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 25, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Jun 08, 2016	Variant summary: The IDS c.438C>T (p.Thr146Thr) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 24360/87524 control chromosomes (including 2605 homozygotes and 9302 hemizygotes) at a frequency of 0.2783237, which is approximately 96 times the estimated maximal expected allele frequency of a pathogenic IDS variant (0.0028868). Thus this variant is a common polymorphism found in the general population. In addition, multiple clinical diagnostic laboratories have classified this variant as benign and the variant is considered a common polymorphism in the literature. Taken together, this variant is classified as Benign. -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 03, 2016	- -

Mucopolysaccharidosis, MPS-II

Benign:4

Benign, criteria provided, single submitter	research	IIFP, CONICET-UNLP	May 31, 2007	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 24, 2014

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

1.5

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over